RagC phosphorylation autoregulates mTOR complex 1

Yang, Guang, Humphrey, Sean J., Murashige, Danielle S., Francis, Deanne, Wang, Qiao‐Ping, Cooke, Kristen C., Neely, G. Gregory, and James, David E. (2019) RagC phosphorylation autoregulates mTOR complex 1. The EMBO Journal, 38. e99548.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website: https://doi.org/10.15252/embj.201899548


The mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) controls cell growth, proliferation, and metabolism in response to diverse stimuli. Two major parallel pathways are implicated in mTORC1 regulation including a growth factor-responsive pathway mediated via TSC2/Rheb and an amino acid-responsive pathway mediated via the Rag GTPases. Here, we identify and characterize three highly conserved growth factor-responsive phosphorylation sites on RagC, a component of the Rag heterodimer, implicating cross talk between amino acid and growth factor-mediated regulation of mTORC1. We find that RagC phosphorylation is associated with destabilization of mTORC1 and is essential for both growth factor and amino acid-induced mTORC1 activation. Functionally, RagC phosphorylation suppresses starvation-induced autophagy, and genetic studies in Drosophila reveal that RagC phosphorylation plays an essential role in regulation of cell growth. Finally, we identify mTORC1 as the upstream kinase of RagC on S21. Our data highlight the importance of RagC phosphorylation in its function and identify a previously unappreciated auto-regulatory mechanism of mTORC1 activity.

Item ID: 73613
Item Type: Article (Research - C1)
ISSN: 1460-2075
Copyright Information: © 2018 The Authors
Date Deposited: 23 May 2022 02:27
FoR Codes: 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310103 Cell metabolism @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
Downloads: Total: 1
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page